The present invention broadly relates to a sampling apparatus for biological reactors and which has a microfilter which is connectable with a bioreactor that is connected to a conduit or connection means for sampling.
Such sampling apparatus are especially provided for the determination of the presence of soluble substances such as nutrient media, metabolites and reaction products, and the concentrations thereof. The measurement of these parameters --aside from the already classical parameters such as temperature, pH-value, oxygen content, CO.sub.2 -content, and so forth - allows improved control of biological processes.
This trend is today further supported by the employment of microprocessors. This is, however, only possible if all measurements can be taken on-line in order to continuously and quickly be able to receive all measurement data which are necessary for process control. New means or devices have already been developed for specific parameters, such as, for example, enzyme electrodes or measurement probes with silicon membranes, which however, are very product-specific and are not directly usable in a bioreactor, partially for reasons of sterility.
In order to overcome this problem, a sampling apparatus of the previously mentioned type has recently been proposed in which continuous sampling is performed by means of a microfiltration system which is traversed by material in the reactor and which is connected to a measuring system.
A description of existing new systems can be found, for example, in:
A. Dincer et al (1984), Developments in Industrial Microbiology 25, page 603; and
Kempe and Schallenberger (1983), Process Biochemistry, December, page 7.
A great disadvantage of the suggested sampling apparatus is that the sampling occurs or takes place in an external loop. This requires the construction of sampling systems with pumps, connection and return lines or conduits and separation devices which are especially developed for this purpose. In addition to this, the absolutely necessary sterilization of these external systems is problematic. Furthermore, the removed sample quantity is relatively large.
The employment of microfiltration membranes in situ in bioreactors has hitherto been described only for the continuous removal of the desired end products (cf. European Patent No. 7133-A).